Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase
Lin, Xin1,2,3; Tian, Dongsong1,2; Fu, Yanhui5; Li, Yanan1,2; Huang, Liejun1,2; Gu, Wei1,2; Song, Jialei1,2; Li, Yanmei1,2; Ben-David, Yaacov1,2; Wen, Min1,2,3; Yuan, Chunmao1,2; Hao, Xiaojiang1,2,4
2019-01-15
Source PublicationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN0223-5234
Volume162Pages:765-780
AbstractThe mixture of GX (guttiferone E and xanthochymol), an inseparable polycyclic polyprenylated acylphloroglucinol (PPAP), showed moderate cytotoxic activities. The chemical transformation of GX yielded three different types of PPAPs (1, 2, and 3/4). A series of analogs were prepared, and the structures of the 40 newly synthesized compounds were elucidated by 1D and 2D NMR and HR-ESI-MS. The derivatives were screened in vitro for antiproliferative activity against five human cancer cell lines: human leukemic cell lines (HEL and K562), cervical cancer cell line (Hela), human breast adenocarcinoma cell line (MCF-7), and human non-small cell lung cancer cell line (A549), using the MTT assay, and most of the derivatives showed good cytotoxic activities. Noticeably, compound 2, a novel tautomer with a hemiketal, exhibited selective cytotoxic activities against HEL (IC50 = 4.79 +/- 0.23 mu M) and K562 (IC50 = 7.69 +/- 0.34 mu M) leukemia cells. The mechanism studies indicated that compound 2 induced apoptosis and arrested the cell cycle at the G0/G1 phase in the HEL cell line. Furthermore, compound 2 activated the intrinsic pathway by reducing the expression of anti-apoptotic protein Bcl-2 and cell cycle-specific cyclin D1 and by enhancing the pro-apoptotic protein Bax. Moreover, the caspase-3 and PPRP1 levels were also upregulated. Our present results suggest that compound 2 is a potential candidate for developing novel anti-leukemia agents in the future. (C) 2018 Elsevier Masson SAS. All rights reserved.
KeywordPolycyclic polyprenylated acylphloroglucinol Chemical transformation Cytotoxicity Cell apoptosis Cell cycle arrest
Indexed BySCI
Language英语
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/64193
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorWen, Min; Yuan, Chunmao; Hao, Xiaojiang
Affiliation1.Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang 550014, Guizhou, Peoples R China
2.Chinese Acad Sci, Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550014, Guizhou, Peoples R China
3.Guizhou Med Univ, Coll Basic Med, Guiyang 550004, Guizhou, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
5.Hainan Normal Univ, Minist Educ, Key Lab Trop Med Plant Chem, Haikou 571158, Hainan, Peoples R China
Recommended Citation
GB/T 7714
Lin, Xin,Tian, Dongsong,Fu, Yanhui,et al. Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,162:765-780.
APA Lin, Xin.,Tian, Dongsong.,Fu, Yanhui.,Li, Yanan.,Huang, Liejun.,...&Hao, Xiaojiang.(2019).Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,162,765-780.
MLA Lin, Xin,et al."Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 162(2019):765-780.
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